Reviews & Analysis

How chromosomes are positioned and folded within the nucleus has implications for gene regulation. In this Review, Kempfer and Pombo describe and evaluate methods for studying chromosome architecture and outline the insights they are providing about nuclear organization.

In this Perspective article, Cheetham, Faulkner and Dinger describe our latest understanding of pseudogenes, which are typically defined as defective copies of regular genes. They argue that being open minded about potential functionality, as well as carefully designing functional studies, will lead to a growing appreciation of emerging functional roles of these understudied elements.

Cell-free gene expression systems have long been used to address fundamental research questions. Now, owing to technological advances, these systems are finding wider applications in the field of synthetic biology, including in biosensing, biomanufacturing, education and the design of gene networks.

Advances in sequencing- and imaging-based techniques for chromosome structure analysis have led to a mature understanding of bacterial chromosome structure and dynamics. In this Review, Dame, Rashid and Grainger discuss the hierarchical nature of bacterial chromosome structure and how it is influenced by diverse types of nucleoid-associated proteins. Furthermore, they describe roles for nucleoid-associated proteins and chromosome structure, including in gene expression, chromosome segregation and cell cycle regulation.

Recent methodological advances have driven the identification and characterization of cis-acting long non-coding RNAs (lncRNAs), which modulate target gene expression through various mechanisms and operate at various genomic distances. This Review discusses recent insights into the evolution and functions of these cis-acting lncRNAs.

To map the full extent of structural variation in the human genome, detection methods are needed that improve on short-read approaches. This Review discusses how ensemble algorithms and emerging sequencing technologies are helping to resolve the full spectrum of structural variations.

Bringing together different strands of genetic research, including results from recent large-scale genome-wide association studies relevant to human ageing, the authors highlight how genetics can further our understanding of the underlying mechanisms of ageing.

This Review discusses the potential of DNA for creating machines that are both encoded by and built from DNA molecules. Alongside an overview of DNA nanostructure assembly, the authors describe recent advances and the remaining challenges, highlighting applications of custom DNA nanostructures as scientific tools.

Incessant encounters of all cellular life forms with mobile genetic elements (MGEs) have driven the evolution of diverse defence mechanisms, including CRISPR–Cas and restriction–modification systems. In this Perspective, Koonin, Makarova, Wolf and Krupovic describe the surprisingly intricate interplay between MGEs and host defence systems. Not only do defence systems commonly show high horizontal mobility but many molecular components are ‘guns for hire’ that have been co-opted by defence systems from MGEs and vice versa.

The increased adoption of DNA sequencing in genetic association studies is uncovering a wide range of population genetic variation, including rare genetic variants. Although this rarity limits the statistical power of associating individual rare variants with phenotypes, this Review discusses the diverse methods for leveraging the collective effects of rare variants in order to uncover important roles in complex traits, particularly human diseases.

Activating transcriptional regulatory elements have traditionally been categorized into promoters, which define transcription start sites, and enhancers, which act distally to stimulate transcription. In this Review, Andersson and Sandelin discuss the latest findings from methodologies for profiling and testing transcriptional regulatory elements at scale. They explain how the data support an updated, nuanced model that accounts for the numerous overlapping molecular properties of promoters and enhancers.

Aneuploidy contributes to tumorigenesis, but the underlying processes are not well understood. This Review explains the context dependency of aneuploidy in cancer and discusses its clinical potential as a prognostic marker and a therapeutic target.

This Review summarizes our current understanding of the molecular, genetic and epigenetic regulation of normal placentation, largely based on insights from the mouse model, and outlines the new opportunities provided by recent successes in deriving human trophoblast stem cells.

Whole-genome sequencing efforts have driven our understanding of transposable elements as a source of genetic variation and the focus is now shifting to understanding their expression and regulation. This Review summarizes the possible functional consequences of transposable element insertion and retention in the genome over time, with a focus on how mobile elements cause disease.

The interactions between tumours and the immune system are highly complex. This article discusses methods — primarily computational tools — for characterizing diverse aspects of cancer–immune cell interactions, including antigen presentation, T cell repertoires and heterogeneity in cell types and cell states. The Review particularly highlights the insights from single-cell data from both sequencing technologies and in situ imaging of tissues.

In a recent declaration, 21 European countries committed to sharing data on at least 1 million human genomes by 2022. This Roadmap emphasizes the challenges of genomic data sharing across borders and how European research infrastructures can support the rapid implementation of transnational access to genomic data.

This Review provides an overview of different approaches for measuring nascent RNA synthesis. It discusses the complementary strengths of these different methods and how they have contributed to a mechanistic understanding of transcription regulation.

In eukaryotes, circular RNAs (circRNAs) carry out important biological roles by acting as microRNA or protein sponges, regulating protein function or through cap-independent translation. New technologies for identifying and characterizing circRNAs will increase our knowledge of their biogenesis and function in health and disease.

The cGAS–STING pathway forms a major DNA-sensing mechanism in mammalian cells. This Review summarizes the current knowledge of cGAS–STING signalling and regulation, highlighting emerging evidence of its role in monogenic inflammatory diseases and cancer and new therapeutic opportunities.

This Review discusses advances in RNA-sequencing technologies and methods over the past decade and outlines adaptations that are enabling a fuller understanding of RNA biology, from when and where an RNA is expressed to the structures it adopts.